Fibrinolytic-deficiencies predispose hosts to septicemia from a catheter-associated UTI.

Autor: Molina JJ; Integrated Biomedical Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA.; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Kohler KN; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Gager C; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Andersen MJ; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Wongso E; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Lucas ER; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Paik A; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA., Xu W; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO, 63110, USA., Donahue DL; W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, USA.; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA., Bergeron K; Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA., Klim A; Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA., Caparon MG; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO, 63110, USA., Hultgren SJ; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO, 63110, USA., Desai A; Department of Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA.; Department of Urology, University of Washington Medical Center, Seattle, WA, 98133-9733, USA., Ploplis VA; W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, USA.; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA., Flick MJ; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA.; UNC Blood Research Center, University of North Carolina, Chapel Hill, NC, 27599, USA., Castellino FJ; W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, USA.; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA., Flores-Mireles AL; Integrated Biomedical Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA. afloresm@nd.edu.; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, 46556, USA. afloresm@nd.edu.; W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN, 46556, USA. afloresm@nd.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Mar 27; Vol. 15 (1), pp. 2704. Date of Electronic Publication: 2024 Mar 27.
DOI: 10.1038/s41467-024-46974-6
Abstrakt: Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections worldwide and are difficult to treat partly due to development of multidrug-resistance from CAUTI-related pathogens. Importantly, CAUTI often leads to secondary bloodstream infections and death. A major challenge is to predict when patients will develop CAUTIs and which populations are at-risk for bloodstream infections. Catheter-induced inflammation promotes fibrinogen (Fg) and fibrin accumulation in the bladder which are exploited as a biofilm formation platform by CAUTI pathogens. Using our established mouse model of CAUTI, here we identified that host populations exhibiting either genetic or acquired fibrinolytic-deficiencies, inducing fibrin deposition in the catheterized bladder, are predisposed to severe CAUTI and septicemia by diverse uropathogens in mono- and poly-microbial infections. Furthermore, here we found that Enterococcus faecalis, a prevalent CAUTI pathogen, uses the secreted protease, SprE, to induce fibrin accumulation and create a niche ideal for growth, biofilm formation, and persistence during CAUTI.
(© 2024. The Author(s).)
Databáze: MEDLINE
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